EPO published application 85301540.2, publication number 154,550, discloses MAb 47D10 and fragments thereof, and diagnostic and therapeutic processes employing the antibody or fragments. The antibody was produced by the hybridoma technique of Kohler and Milstein, using A549 lung adenocarcinoma cells as immunogen and for ELISA screening of hybridoma supernatants. The hybridoma designated 47D10 was selected with significantly greater reactivity for the immunogen A549 than normal embryonic lung fibroblast cells. Hybridoma 47D10 is on deposit in the American Type Culture Collection with accession number HB8504, under the terms of the Budapest Treaty.
The above EPO application reports results of ELISA tests of 47D10 hybridoma supernatant for reactivity with various fixed normal and tumor cell lines as well as results of ELISA tests of purified 47D10 MAb with live cells of the same normal and tumor lines. The results showed significant antibody binding to the immunogen A549 and a colon adenocarcinoma cell line, but only slight reactivity with breast carcinoma and melanoma lines.
The EPO application also reports results of immunohistochemical studies of 47D10 MAb on a variety of normal and neoplastic tissues. The antibody reacted with 38 of 40 pancreatic adenocarcinomas, 5 of 8 lung adenocarcinomas, 8 of 11 colon adenocarcinomas and 4 of 7 breast infiltrating ductal carcinomas. However, a colon adenocarcinoma metastatic to liver and a breast adenocarcinoma did not react with the antibody. Normal tissues, pancreas tissue with pancreatitis, breast tissue with fibrocystic disease and ovarian cystadenomas did not react. Metastatic pancreatic tumor cells were detected in lymph nodes by the antibody.
It is stated in the EPO application that 47D10 MAb is useful in the diagnosis of primary and metastatic pancreatic tumor cells by conventional in vivo diagnostic methods and also by conventional in vitro diagnostic procedures such as the assay of human blood samples or other body fluids.
Ho et al., Fed. Proc. 45, 984 (1986) reports that the 47D10 tumor-associated antigen is a group of surface glycoproteins of 63-97 Kd (average 85 Kd) molecular weight. However, it is now known that the antigen is a group of surface glyco proteins ranging in molecular weight from 67 Kd to 98 Kd. EPO publication 154,550 and the Ho et al. article are incorporated herein by reference.
Serum and plasma assays to detect other tumor-associated antigens have been reported. Ceriani et al., Proc. Nat'l. Acad. Sci., 79, 5420-5424 (1982) reports the presence of high levels of 150 Kd, 70 Kd and 46 Kd human mammary epithelial antigens in sera of breast cancer patients and a monoclonal antibody Mc 3 to the 46 Kd antigen raised against human milkfat globule membrane. PCT Publication Number WO 85/02411 reports a monoclonal antibody 3 El-2 raised against ductal breast carcinoma cells which detects an antigen present in elevated levels in the serum of patients with carcinoma of the breast. EPO Publication Number 160446 reports a 330 Kd antigen which is shed by breast cancer cells, monoclonal antibodies 21DD5 and 21DD7 to the antigen raised against breast carcinoma cells, and use of the monoclonals in a plasma assay to detect breast cancer. Goodall et al., Br. J. Cancer, 52, 177-182 (1985) reports work to establish an assay for detection of Ca antigen in sera of breast cancer patients, states that presence of Ca antigen in serum had no diagnostic significance, but indicates that assay of sequential serum samples could be of prognostic value since sera of half of patients with metastatic spread had elevated levels of the antigen. Hayes et al., J. Clin. Invest, 75, 1671-1678 (1985) reports a mouse monoclonal antibody DF3 prepared against a membrane-enriched fraction of a human breast carcinoma which reacts with a 300 Kd mammary epithelial antigen, and use of the antibody for detection the antigen in plasma of breast cancer patients. Hilkeus et al., Cancer Research, 46, 2582-2587 (May, 1986) reports use of monoclonal antibody 115D8, raised against human milkfat globule membranes, in a radioimmunoassay to detect elevated levels of MAM-6, a &gt;400 Kd epithelial membrane antigen, in sera of breast cancer patients.
Herlyn et al. J. Clin. Immunology, 2, 135-140 reports monoclonal antibodies 19-9, 52a and C.sub.4 14 raised against colon carcinoma cell lines and their use in a serum assay to detect colorectal, gastric and pancreatic carcinoma. The antigen detected by two of these antibodies is reported to be a monosialoganglioside. Haglund et al., Br. J. Cancer, 53, 197-202 (1986) also reports evaluation of antibody 19-9 in a serum assay for pancreatic cancer. EPO publication Number 171,083 discloses monoclonal antibodies KMO1 and KMO2 raised against a 700-1,500 Kd fraction of a colon cancer cell line, and their use in a serum assay to detect pancreas, colon and liver cancer.
Klug et al. Cancer Research, 44, 1048-1053 (1984) reports use of a murine monoclonal antibody OC125 in an immunoradiometric serum assay for an ovarian carcinoma associated antigen CA125.